Author

Defense Date

2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Human Genetics

First Advisor

Dr. Colleen Jackson-Cook

Abstract

Breast Cancer (BC) is one of the most commonly diagnosed malignancies in females. The 5-year survival rate for women with early stage BC is about 90%. However, the quality of life (QOL) for many of these women may be adversely affected due to treatment/cancer–related side effects, including a constellation of symptoms (anxiety, depression, pain, fatigue, sleep disturbance and depression), that are collectively termed psychoneurological symptoms (PNS). To gain insight into the contributory role of telomere length (TL) in the development and persistence of PNS, we have longitudinally studied 72 women (ages 23-71) with early stage BC (I-IIIA) at 5 time points: prior to chemotherapy (baseline), prior to the fourth cycle of chemotherapy (mid-chemo), 6 months, 1 year and 2 years following the initiation of chemotherapy. Measures quantified included TL [using both a monochrome multiplex qPCR assay (at 5 time points) and a semi- quantitative chromosome-specific fluorescence in situ hybridization (FISH) assay (at baseline and mid-chemo)] and scores for each PNS. Variables predictive of qPCR mean TLs were age (p=0.004) and race (African Americans had greater mean TLs than Caucasians; p=0.019). While visit was not found to be a significant predictor of mean TLs (p=0.666), chromosome-specific TL shortening was observed at mid-chemo for 1p (p =0.022), 5q (p = 0.041), 7q (p =0.025), 9q (p =0.045), 18q (p =0.002), 20p (p =0.020), 21q (p =0.040) and 22p (p =0.025). Type of chemotherapy was shown to be a significant predictor of both mean TLs (TAC significantly greater than TCH; p= 0.036) and chromosome-specific TLs for 32 of the 46 chromosomal arms (p=0.004 to 0.049). Pain was found to be a significant negative predictor of chromosome- specific TLs (higher pain; shorter telomeres) for 5q (p=0.040), 8p (p=0.047), 13p (p=0.019), 20p (p=0.036), 22p (p=0.035), Xp (p=0.014), Xq (p=0.039). Expanding upon the knowledge gained from this study offers hope for the future development of biomarkers that could identify patients at risk for PNS and improve their QOL.